title: Hypothesis: Persistently elevated hCG causes gestational ovarian overstimulation associated with prolonged postpartum hyperandrogenism in mothers of aromatase-deficient babies.
abstract: BACKGROUND
  Aromatase deficiency due to a CYP19A1 defect leads to fetoplacental inability to convert androgens into estrogens. Pregnant mothers experience virilization caused by excess nonaromatized fetal androgens entering the maternal circulation. Biochemical normalization is believed to take place shortly after delivery.
  
  
  OBJECTIVE
  We report prolonged postnatal hyperandrogenism and enlarged multicystic ovaries in the mother of an affected 46,XX infant and hypothesize a possible pathogenetic mechanism.
  
  
  METHODS
  We investigated the mother on days 12 and 20 after delivery. FSH, LH, T, estradiol (E2), androstenedione (A), dehydroepiandrosterone-sulfate (DHEA-S), and human chorionic gonadotropin (hCG) plasma levels were obtained, and ovarian ultrasonography and magnetic resonance imaging were performed.
  
  
  RESULTS
  T (1040 ng/dL), A (6940 ng/dL), and E2 (2787 pg/mL) levels were markedly elevated on day 12 after delivery, whereas LH and FSH were suppressed (<0.1 IU/L). On day 20, all hormones had decreased significantly; however, T, A, and E2 still remained 3.5-, 2.2-, and 1.4-fold elevated, respectively, as compared to upper reference values. hCG (18.9 U/L) was still increased. DHEA-S was normal on both occasions. Sonography and magnetic resonance imaging revealed enlarged ovaries, with several cysts up to 4 cm. There was no history of polycystic ovary syndrome.
  
  
  CONCLUSIONS
  We hypothesize that persistent ovarian overstimulation by hCG had occurred in the mother during pregnancy, leading to prolonged autonomous excess production of androgens during the first weeks after delivery. As a causative mechanism, we propose that gestational hyperandrogenism and hypoestrogenism reduced inhibition of placental GnRH and hCG secretion by progesterone, resulting in persistently elevated hCG.
authors.affiliation: Division of Pediatric Pulmology, Allergology, and Endocrinology, Department of Pediatrics, Medical University of Vienna, 1090 Vienna, Austria. stefan.riedl@meduniwien.ac.at
authors.forename: Stefan
authors.initials: S
authors.lastname: Riedl
authors.forename: Alexander
authors.initials: A
authors.lastname: Springer
authors.forename: Gabriele
authors.initials: G
authors.lastname: Häusler
authors.forename: Glynis
authors.initials: G
authors.lastname: Price
authors.forename: Annette
authors.initials: A
authors.lastname: Richter-Unruh
authors.forename: Elisabet
authors.initials: E
authors.lastname: Stener-Victorin
authors.forename: Stefan A
authors.initials: SA
authors.lastname: Wudy
mesh_terms: D058489:46, XX Disorders of Sex Development / Q000150:complications*; D001141:Aromatase / Q000172:deficiency; D006063:Chorionic Gonadotropin / Q000097:blood*; D005260:Female; D006177:Gynecomastia / Q000150:complications*; D006801:Humans; D017588:Hyperandrogenism / Q000209:etiology*; D007231:Infant, Newborn; D007248:Infertility, Male / Q000150:complications*; D008297:Male; D008661:Metabolism, Inborn Errors / Q000150:complications*; D016471:Ovarian Hyperstimulation Syndrome / Q000150:complications*; D049590:Postpartum Period; D011247:Pregnancy; D011248:Pregnancy Complications; D014770:Virilism / Q000209:etiology
chemical_list: D006063:Chorionic Gonadotropin; D001141:Aromatase